Vertex Pharmaceuticals Incorporated

7- or 8-hydroxy-isoquinoline and 7- or 8-hydroxy-quinoline derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD).

Compounds of formula I and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.

Macroencapsulation devices and their methods of use are disclosed. In one embodiment, a macroencapsulation device may include a first outer membrane, a second outer membrane, and at least one semipermeable membrane disposed there between to form at least a primary compartment configured to house a first population of cells and a secondary compartment in fluid communication with the primary compartment through the first semipermeable membrane. In some embodiments, the flow of material into and out of the compartments of the macroencapsulation device and/or the application of an appropriate pressure differential between the compartments may be used to control the flow of filtrates, ancillary agents, and other materials between the compartments of the device when positioned in vivo.

The disclosure features methods of correcting a mutation in the human beta-globin (HBB) gene in a cell or population of cells. The disclosure also features methods of increasing repair of a DNA double stranded break (DSB) in an HBB gene by the homology-directed repair (HDR) pathway. The disclosure also features compositions for use in the methods.

Macroencapsulation implantation systems and containers for storing and transporting a macroencapsulation device disposed within an end effector as well as related methods are described. In some embodiments, a macroencapsulation implantation system may include a handle that is configured to be selectively engaged with an elongated shaft including an end effector in which a macroencapsulation device may be disposed. In some embodiments, a container may be configured to maintain an end effector, and a macroencapsulation device disposed therein, in a desired pose within an internal volume of the container using an appropriately configured support. In some embodiments, the container may include an appropriately sized and shaped seal between a lid and container such that the container is biased towards an open configuration.

Provided are materials and methods for treating patients with hemoglobinopathies, either ex vivo or in vivo. Also provided are materials and methods for deleting and/or mutating a portion of a human beta globin locus on chromosome 11 and one or more of: a BCL11 A gene on chromosome 2, and a DNA sequence that encodes a transcriptional control region of the BCL11 A gene on chromosome 2, in a human cell by genome editing and thereby increasing the production of fetal hemoglobin (HbF) in the genome-edited human cells.

Disclosed herein are compositions and methods of enhancing stem cell differentiation into beta cells with use of one or more epigenetic modification compounds. The present disclosure also relates to compositions and methods of sorting and enriching the differentiated beta cells. The present disclosure also relates to compositions and methods of irradiating cell population for reducing proliferation.

The present disclosure relates to macroencapsulation devices and related methods of manufacture where the membranes of a device may be mounted to an associated frame in a relaxed, or slack, configuration prior to filling with a desired material.

The invention in some embodiments thereof, relates to the field of compositions and/or pharmaceutical compositions comprising one or more biologically active compound, and is directed to methods of using same such as for treating an ApoL1 related disease or a disorder in a subject.

1H-pyrazolo[4,3-g]isoquinoline and 1H-pyrazolo[4,3-g]quinoline derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD).